The present invention generally relates to thromboresistant coatings for medical devices having a blood-contacting surface, as well as to methods for forming such coatings and to the medical devices thus formed More particularly, the invention relates to a polymeric matrix formed from an aminosilane homopolymer or copolymer, this matrix being formed on the surface of a medical device which is intended for contacting blood and the like when in use. An antithrombogenic agent is secured to the matrix to provide the thromboresistant coating.
A well-recognized problem in the medical community is the development of a thrombus or blood clot or obstruction that forms when any of a number of devices are used either within the body or within systems wherein blood or other body fluids are contacted or circulated. Exemplary of medical devices for which this problem is a concern are catheters, vascular grafts, cardiac pacer leads, heart diaphragms, sutures, needles, angioplasty devices, glass beakers, dialysis membranes, filters, sensors, monitors and the like. These types of medical devices will typically exhibit a variety of surfaces that contact blood or other body fluids. Representative materials in this regard include polytetrafluoroethylenes, polyamides, polyesters, polyurethanes, polysiloxanes, polyolefins, metals and the like.
An example of an approach that was directed toward this problem is found in United States Letters U.S. Pat. No. 3,639,141 to Dyck, which is incorporated by reference hereinto. That patent states that plastics are rendered nonthrombogenic by heparinizing them following treatment with an aminosilane in an inert solvent which preferably swells the plastic. A preliminary treatment with sodium is taught. The Dyck patent teaches immersing the plastic component in silane solution, washed in pure solvent and immersed in a heparin solution. No suggestion is made to form a matrix of polymerized aminosilane for receiving a thromboresistant material such as a heparinous material, and no suggestion is made concerning reacting a thromboresistant molecule to the amino groups on the aminosilane to provide a non-reversible reaction.
Many other approaches have been taken in the past when responding to the problem of imparting thromboresistant properties to artificial implants, prostheses and other devices for contacting body fluids and the like. They typically are deficient, especially from the point of view of providing an efficient means for securing or adhering the antithrombogenic agent to the fluid-contacting surface.
It has been found that, by proceeding in accordance with the present invention, it is possible to efficiently produce thromboresistant coatings onto surfaces of medical devices through an approach that provides attachment of an antithrombogenic agent in a manner that can be readily controlled so as to achieve a thromboresistant coating that can be reproduced in a consistent manner. In summary, the invention coats the surface of the device that is to be rendered thromboresistant with an aminosilane-containing composition which is then subjected to curing conditions in order to thereby form an aminosilane polymeric matrix. Typically this matrix formation is carried out under controlled time, temperature and humidity conditions until a matrix having the desired physical structure and chemical moieties is provided. Thereafter, an antithrombogenic agent is chemically secured to the aminosilane polymer matrix in order to form the thromboresistant coating onto the fluid-contacting surface of the medical device.
It is a general object of the present invention to provide an improved thromboresistant coating, a medical device having the thromboresistant coating, and a method for preparing same.
Another object of the present invention is to provide an improved thromboresistant coating, article and method which utilize a three-dimensional matrix containing aminosilanes for securely attaching antithrombogenic agents to a surface intended for contacting blood and the like.
Another object of the present invention is to provide an improved thromboresistant coating, article and method which allow for attachment of antithrombogenic agents to surfaces of prostheses and other medical devices in a controlled and efficient manner.
Another object of this invention is to provide an improved thromboresistant coating, device and method which can exhibit a desired hydrophilicity.
Another object of the present invention is to provide an improved thromboresistant coating, device and method which can be adjusted in order to achieve a desired degree of uptake and elution of the antithrombogenic agent.
Another object of this invention is to provide an improved thromboresistant coating, device and method which can provide a coating having improved elastomeric properties.
Another object of the present invention is to provide an improved thromboresistant coating, device and method which can provide an increased extent of drug loading onto and/or into the coating.
Another object of the present invention is to provide a thromboresistant coating, device and method which provide a three-dimensional matrix that is cured as a film substantially thicker than that typically found when silane priming agents or coupling agents are used.
Another object of the present invention is to provide a thromboresistant coating, device and method which utilize a coupling component applied without a solvent or only minimal amounts of a solvent.
These and other objects, features and advantages of this invention will be clearly understood through a consideration of the following detailed description.